Prostate cancer (CaP) is the most commonly diagnosed male cancer in the United States. This year, over thirty thousand American are expected to die of androgen-independent metastatic CaP. The Prostate Cancer Program is composed of four highly interactive themes: 1) the molecular pathogenesis of CaP, 2) enhancing therapeutic response, 3) chemoprevention, and 4) clinical research. The theme of molecular pathogenesis is central to the Program. Extensive molecular biology investigations are ongoing within three focal areas: 1) tumor suppressor genes, 2) hormone receptors, and 3) tyrosine kinases. The second, theme, enhancing therapeutic response, is focusing on the areas of radiation therapy and systemic therapy. Since enhance therapeutic response, is focused on the areas of radiation therapy and systemic therapy. Since 90% of those diagnosed with CaP have localized disease, if the effectiveness of radiation therapy could be enhanced, more men could avoid surgery. Additionally, if mechanisms to increase apoptosis in CaP can be identified, this approach would render systemic therapy more effective. The third theme, chemoprevention, is favored by the high prevalence of CaP and its long natural history, making it ideal for this type of intervention. The strong focus on nutrition in the Cancer Program makes, this prostate Cancer Program ideally situated to pursue chemoprevention. One difficulty in such studies is determining the effectiveness of specific compounds. The expertise of our collaboratory colleagues at the Lawrence Livermore National Laboratory (LLNL) in accelerator mass spectrometry (AMS) analysis of DNA adducts has the potential to overcome this limitation. Finally, since the ultimate direction of the investigations within the Program is to improve patient care, the fourth theme is clinical research. The group has a longstanding presence in phase I and II trials and in phase III national trials and has expertise in conducting molecular correlative studies. The described efforts address the following goals: 1) To identify molecular abnormalities in CaPs, 2) to define the biological consequences of the abnormalities, 3) to assess their functional roles in response to therapy, and 4) to develop new strategies for prevention and treatment of CaP. Thus, this Prostate Cancer Program demonstrates a comprehensive, disease-specific effort among the members of the Cancer Center.